| First Author | Vacaru AM | Year | 2010 |
| Journal | FEBS J | Volume | 277 |
| Issue | 6 | Pages | 1562-70 |
| PubMed ID | 20158519 | Mgi Jnum | J:200378 |
| Mgi Id | MGI:5508572 | Doi | 10.1111/j.1742-4658.2010.07584.x |
| Citation | Vacaru AM, et al. (2010) Catalytically active membrane-distal phosphatase domain of receptor protein-tyrosine phosphatase alpha is required for Src activation. FEBS J 277(6):1562-70 |
| abstractText | Receptor protein-tyrosine phosphatase alpha (RPTPalpha) is a transmembrane protein with tandem cytoplasmic phosphatase domains. Most of the catalytic activity is contained by the membrane-proximal catalytic domain (D1). We found a spontaneous Arg554 to His mutation in the pTyr recognition loop of the membrane-distal phosphatase domain (D2) of a human patient. This mutation was not linked to the disease. Here, we report that the R554H mutation abolished RPTPalpha-D2 catalytic activity. The R554H mutation impaired Src binding to RPTPalpha. RPTPalpha, with a catalytic site cysteine to serine mutation in D2, also displayed diminished binding to Src. Concomitant with decreased Src binding of the R554H and C723S mutants compared with wild-type RPTPalpha, enhanced phosphorylation of the inhibitory Src Tyr527 site was observed, as well as reduced Src activation. To confirm that catalytic activity of RPTPalpha-D2 was required for these effects, we analyzed a third mutant, RPTPalpha-R729K, which had an inactive D2. Again, Src binding was reduced and Tyr527 phosphorylation was enhanced. Our results suggest that a catalytically active D2 is required for RPTPalpha to bind and dephosphorylate its well-characterized substrate, Src. |
